The objective is to characterize some biochemical and genetic mechanisms of obligate intracellular parasitism of eukaryotic cells by Coxiella burnetii, the etiological agent of Q fever. This organism grows in the phagolysosomal milieu of eukaryotic cells. Thus, it resists the microbicidal mechanisms of this compartment. Previous studies have described a pathogenic mechanism of acid activation which leads to substrate transport and metabolism. More recently we have shown that in vitro protein synthesis occurs during axenic cultivation. However, multiplication of C. burnetii in complex media has not been achieved at this time. Some resistance properties of C. burnetii have been correlated with protease resistant proteins associated noncovalently and covalently to the peptidoglycan. Lysozyme hydrolysis of the polysaccharide portion of the peptidoglycan does not result in dissolution of the sacculus thereby conferring some resistance to microbicidal mechanisms. Moreover, stability of the peptidoglycan-protein complex may be enhanced by protein-protein and protein-peptidoglycan interactions between covalently- and non-covalently-band proteins which are resistant to proteolysis. Phase specific monoclonal antibodies have been isolated which recognize phase I (virulent) or phase II (avirulent) cells. An objective is to use these monoclonals to monitor the frequency distribution of the phase variants. Perhaps we can understand some of the genetics involved in conferring resistance properties to C. burnetii. Future investigations into the molecular biology of C. burnetii will be carried out at the U.S. Army Medical Research Institute of Infectious Diseases, Frederick, Maryland.